. Author manuscript; available in PMC: 2015 Nov 1.

Published in final edited form as: Rheum Dis Clin North Am. 2014 Sep 2;40(4):637–657. doi: 10.1016/j.rdc.2014.07.005

Table 3.

Selected genetic, environment, and gene-environment interactions in RA, SLE, and AS.

Phenotype	MHC gene (variance explained)	Number of non-HLA SNPs associated ^Ref	Selected non-HLA genes/loci	Key environmental factors	Proposed gene-environment interactions
RA	HLA-DRB1 HLA-DPB1 HLA-B (12%)	101⁴	PTPN22 TNAIF3 TYK2	Cigarette smoking Reproductive factors and hormonal exposures Silica Periodontitis Excess body mass Alcohol intake Fish intake	HLA-DRB1-smoking PTPN22- smoking
SLE	HLA-DRB1 HLA-DPB1 HLA-G	>40⁸⁶	ATG5 TREX1 DNASE1 IRF5 TLR7 FCGR2A	Ultraviolet-B light Current cigarette smoking Silica Reproductive factors and hormonal exposures Alcohol intake Epstein-Barr virus	DNA repair genes-UV-B light and smoking TLR genes-infections
AS	HLA-B27 (20%)	30¹⁰⁸	IL23R IL1R2 2p15	Gut microbiome Cigarette smoking Testosterone	HLA-B27-infections

Abbreviations: AS, ankylosing spondylitis; HLA, human leukocyte antigen; MHC, major histocompatibility complex; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SNPs, single nucleotide polymorphisms; TLR, toll-like receptor; UV-B, ultraviolet-B.